—of drugs in British Columbia was attributable to the introduction of new products or new indications that contribute nothing or little in therapeutic terms. These products, which are called me-too products, are equivalent molecules to those already found on the market. The efficacy of these new indications is often not tested in the field. Consumption of new products that have replaced old ones doubled drug expenditures in British Columbia between 1996 and 2003.
According to the Patented Medicine Prices Review Board, between 1990 and 2003, only 5.9% of these new products were breakthroughs in therapeutic terms. That is the worst of it. Likewise, the FDA reported that three-quarters of the drugs put on the market in the 1990s had nothing new to offer over old treatments.
The foregoing shows the importance of a rigorous review of the drugs appearing in provincial formularies, that is, a probing and pertinent review conducted by independent experts. A study published in the Journal of the American Medical Association, involving 1,140 clinical trials, indicated that trials funded by the industry were 3.6 times more likely to result in conclusions favourable to the sponsor’s product. These are the studies that are submitted to the control agencies for approval.
For example, let us highlight the new antihypertensives proposed as first-line treatment, which are no more useful for the vast majority of people than the old drugs, but which cost infinitely more. Dr. Furberg, a senior researcher in a huge study done on antihypertensives, has calculated that American consumers have spent from $8 to 10 billion unnecessarily on these new products.
Mr. Robert Goyer, former head of the Conseil du médicament du Québec, estimated that the most popular and most expensive antiulcerant cost $60 million too much, since less expensive alternatives were available and were just as effective in most cases.
The Green Cross has also reported the existence of major differences in the prices of drugs paid by various government agencies. The cost of one drug in the Ontario formulary was entered as $1.90 and the same product was sold to the Department of Defence for 45¢. Four times as much.
New Zealand is showing us the way for optimum drug use. In 1973, this country set up a Crown entity, Pharmac, made up of independent scientists and groups of patients. Pharmac is a group pharmaceutical buying centre that can negotiate prices. Through competitive bidding among manufacturers, it causes them to compete with one another.
Pharmac prepares a list of the best drugs on the basis of scientific criteria. It chooses the one that that will become the reference product and selects a number of alternatives, which are reimbursed at the price of the cheapest reference product, except in cases of intolerance or contraindications. Agreements called cross-deals are negotiated with manufacturers. When a new effective and safe drug arrives on the market, it is entered in the formulary, provided the manufacturer agrees to a discount on a product already on the list. Pharmac also practises the system of maximum expenditure. A contract is concluded with a manufacturer with a view to the sale and reimbursement of a certain quantity of drugs based on a needs analysis. If expenditures surpass this maximum, the firm reimburses the difference to Pharmac. Finally, any products that have not demonstrated their superiority over existing treatments are not reimbursed. Such was the case of Celebrex and Vioxx before they were taken off the market on account of their cardiovascular toxicity. Incidentally, Vioxx won the Galien Prize in 1999, I believe, which is really the Oscar of drugs. Thus the New Zealand formulary contains 2,600 products, compared to 5,000 in Quebec.
Allow me to broach a related topic, though one in keeping with the foregoing. The review of drugs begins long before the authorities ask questions about the appropriateness of entering them in the formularies, that is, as soon as they are submitted to the Therapeutic Products Directorate. In this regard, we should hope that improvements are made in the assessment of the effectiveness and safety of drugs.
Are Health Canada’s licensing criteria rigorous enough? For a drug to be approved, it must as a rule show that it is more effective than a placebo. Should it not be required that a product be tested against a drug that is already on the market, whose toxicity profile is already known and that is much less expensive? Furthermore, clinical trials are generally short-lived. They are designed to assess the effectiveness of the drug and not its toxicity, and the patients recruited are ideal patients. The consequences may be dramatic. This is how much later the undesirable effects of numerous products are discovered. Over a 25-year period, 10% of the drugs received the most severe warning from the FDA, the black box warning, and 2.9% were withdrawn from the market, while the monograph for 51% of them was changed on account of the safety problems discovered after they were marketed. The research by Dr. Joel Lexchin, of York University, shows that, over a 40-year period, 39% of the drugs taken out of circulation were removed between 1993 and 2004, a much larger proportion than in previous decades. Were some of them approved too quickly?
Many experts have sounded the alarm about the problem. In the U.S., a lot of literature talks about the credibility gap concerning the drug licensing process, and since the regulatory process is practically identical in both countries, we have cause for concern.
This credibility gap motivated the United States Institute of Medicine to make a whole series of recommendations on the regulatory process. Among these recommendations, the Institute proposed that a black triangle be placed on new drugs for a two-year period in order to indicate that not all the undesirable effects of the product are known; it suggested increasing the FDA budget; it suggested getting rid of what are called user fees, which are the charges manufacturers pay to have new drugs approved. These fees have existed in the United States since 1992 and in Canada since 1994. In exchange, manufacturers obtained a reduction in the approval time for new products. Numerous observers think that, since it was implemented, this practice has been responsible for the increase in the number of drugs withdrawn for safety reasons. One internal FDA survey conducted at the turn of the century stressed that 36% of the Agency’s scientists—they had four answers to choose from—had no confidence or had moderate confidence in the safety and effectiveness of the drugs they approve and 18% said they had been pressured to approve drugs, in spite of the reservations they had concerning their toxicity.
Dr. Robert Peterson, the former Director General of Health Canada, confided to the Canadian Medical Association Journal that international safety regulation is adequate in 75% of cases and that Health Canada does not have any legal powers, notably that of requiring follow-up studies after marketing to check the toxicity of drugs. Most of the phase IV trials requested by Health Canada are simply not carried out. Furthermore, Health Canada is studying proposals to modify the licensing process to emphasize risk management. This raises concerns on the part of numerous observers, fears that were stated in a very recent article in the Canadian Medical Association Journal.
In view of the foregoing, should the principle of precaution not prevail over risk management, particularly since the reviews indicate that 10,000 Canadians die each year from the undesirable effects of drugs, even though they have followed the instructions to the letter?
By way of conclusion, Health Canada should have extended powers and adequate funding to review drugs. Would it not be a good idea to use a few of the millions in our huge surpluses to guarantee a better quality of life and greater safety for Canadian citizens who deserve it? And why not restore the Bureau of Drug Research, which was closed in 1997?
Thank you.